Spatiotemporal components of sustained functional hyperemia are differentially modulated by locomotion and silenced with vascular chemogenetics

Abstract

ABSTRACTNeural activity underlying sensation, movement or cognition drives regional blood flow enhancement – termed functional hyperemia – to increase the oxygen supply to respiring cells for as long as needed to meet energy demands. However, functional hyperemia is often studied under anesthesia which typically yields response profiles that appear temporally and spatially homogenous. We have insufficient understanding of the underlying kinetics of oxygen delivery in awake animals, especially during specific behaviours that may influence neurally-driven enhancements in cerebral blood flow. Using widefield intrinsic optical signal imaging in awake, head-fixed but active mice, we demonstrated distinct early and late components to changes in intravascular oxygenation in response to sustained (30s) whisker stimulation. We found that the late component (20-30s), but not the early component (1-5s), was strongly influenced by level of whisking/locomotion in the region of highest response and in surrounding regions. Optical flow analyses revealed complex yet stereotyped spatial properties of the early and late components that were related to location within the optical window and the initial state of the cerebral vasculature. In attempt to control these complex response characteristics, we drove a canonical microvasculature constriction pathway using mural cell Gq-chemogenetic mice. A low-dose of systemic C21 strongly limited both the magnitude and spatial extent of the sensory-evoked hemodynamic response, showing that functional hyperemia can be severely limited by direct mural cell activation. These data provide new insights into the cerebral microcirculation in the awake state and may have implications for interpreting functional imaging data.